First Author | Zechel S | Year | 2018 |
Journal | Biol Open | Volume | 7 |
Issue | 5 | PubMed ID | 29716946 |
Mgi Jnum | J:262197 | Mgi Id | MGI:6159442 |
Doi | 10.1242/bio.033753 | Citation | Zechel S, et al. (2018) Cell-autonomous role of GFRalpha1 in the development of olfactory bulb GABAergic interneurons. Biol Open 7(5):bio033753 |
abstractText | GFRalpha1, a receptor for glial cell line-derived neurotrophic factor (GDNF), is critical for the development of the main olfactory system. The olfactory bulb (OB) of Gfra1 knockout mice shows significant reductions in the number of olfactory sensory neurons, mitral and tufted cells, as well as all major classes of OB GABAergic interneurons. However, the latter do not express significant levels of GFRalpha1, leaving the mechanism of action of GFRalpha1 in OB interneuron development unexplained. Here we report that GFRalpha1 is highly expressed in the precursor cells that give rise to all major classes of OB interneurons, but is downregulated as these neurons mature. Conditional ablation of GFRalpha1 in embryonic GABAergic cells recapitulated the cell losses observed in global Gfra1 knockouts at birth. GFRalpha1 was also required for the sustained generation and allocation of OB interneurons in adulthood. Conditional loss of GFRalpha1 altered the migratory behaviour of neuroblasts along the rostral migratory stream (RMS) as well as RMS glial tunnel formation. Together, these data indicate that GFRalpha1 functions cell-autonomously in subpopulations of OB interneuron precursors to regulate their generation and allocation in the mammalian OB. |